Field of the Invention
The present invention relates to a useful method for preparing lipid nanocapsules charged with at least one active agent and also to such nanocapsules and the compositions containing them.
Description of the Background
Nanovesicular systems, of nanocapsule or nanodroplet type whose size ranges from 50 to 500 nanometers and which are formed from a liquid or semisolid core surrounded by an outer membrane, are already known. The constituents of their membrane may be synthetic, for example of polymeric, protein or lipid nature like liposomes. Notably, liposomes that have a lamellar structure formed from a stack of lipid layers separated from each, other by aqueous compartments always have an aqueous core.
These nanometric structures have also already been proposed for the purposes of encapsulating active agents either in their aqueous core when the active agent is water-soluble or water-dispersible, or in their lipid layer when the active agent is fat-soluble or fat-dispersible.
For example, U.S. Pat. No. 5,961,970 proposes, as active agent vehicle, oil-in-water emulsions at the submicron scale, i.e. miniemulsions whose droplets have a hydrophobic core of lipid nature and are surface-stabilized with amphiphilic and/or nonionic surfactants like surfactants of phospholipid type. These droplets are thus maintained in suspension in an aqueous phase. This type of submicron emulsion is obtained from a basic emulsion by subjecting it to several successive homogenization cycles at high shear.
U.S. Pat. No. 5,576,016 describes macroemulsions whose droplets are formed from a solid lipid core and which are stabilized with a phospholipid envelope. This phospholipid envelope has a lamellar structure formed from one or more layers of phospholipid molecules like liposomes. A highly hydrophobic active agent may be charged into the core, and a water-soluble active agent may, on the other hand, be incorporated into the aqueous compartments present in the phospholipid envelope.
Moreover, the inventors have also described in patent EP 1 265 698, as vehicle for fat-soluble or fat-dispersible active agents, nanocapsules with a liquid core and a solid shell of lipid nature, and novel technology for gaining access thereto. More specifically, these nanocapsules, charged with fat-soluble or fat-dispersible active agents, are obtained from a microemulsion, this microemulsion being prepared via the technique of phase inversion via a thermal effect (PIT emulsion).
The principle of phase inversion temperature (PIT) emulsification is well known to those skilled in the art; it was described in 1968 by K. Shinoda (J. Chem. Soc. Jpn, 1968, 89, 435). It was shown that this emulsification technique makes it possible to obtain fine stable emulsions (K. Shinoda and H. Saito, J. Colloid Interface Sci., 1969, 30, 258).
This technique makes it especially possible to obtain a mean size of the globules constituting the oily phase ranging from 0.1 to 4 μm (100 to 4000 nm).
However, when these nanocapsules are intended for encapsulating an active agent, this method necessitates having the active substance that it is desired to encapsulate being present right from the first step of the method and therefore the entire method must be carried out in the presence of this active agent. However, this obligation may sometimes be constricting to a person skilled in the art.
Moreover, the nanocapsules obtained have been proposed therein only for the purpose of encapsulating, within their oily core, lipophilic or fat-dispersible active agents. Now, for obvious reasons, it would be advantageous for these nanocapsules also to be usefully employed for encapsulating water-soluble or water-dispersible active agents.
Thus, a person skilled in the art does not have a simple and rapid method of implementation for obtaining nanocapsules charged with active agents, especially active agents having a hydrophilic character and, what is more, a method having an advantageous encapsulation yield.